High performance shape memory foams with isocyanate-modified hydroxyapatite nanoparticles for minimally invasive bone regeneration
Introduction
Shape memory polymers (SMPs) have recently gained attention in biomedical applications, such as smart sutures [1], tissue engineering [2], vascular stents [3], bladder sensors [4] and nerve repairing [5]. The SMPs are smart materials which could recover their original shapes from deformed secondary shapes in response to external stimuli such as heat [6], moisture [7], UV light [8] and magnetic field [9]. This feature permits SMP foams to be implanted into the body in compact secondary shapes through minimally invasive surgery and then recover to their original shapes upon exposure to an external stimulus such as body temperature [1], [10], [11], [12]. Thus, SMP foams used as bone scaffolds are expected to be exploited for the treatment of irregular bone defects.
SMP foams for bone regeneration should mimic mechanical properties and bone morphology, and possess high shape memory efficiency in order to optimize the integration into surrounding tissues and facilitate delivery by minimally invasive surgery. In the first place, bones are composite materials which have high mechanical properties. However, insufficient mechanical integrity has been found in the existing polymers and polymer composites for bone regeneration [13], [14]. Traditional porous polymer composites exhibited compressive stress and modulus in the order of 0.1 MPa and 10 MPa, respectively [13]. These are far lower than those of trabecular bone (compressive stress of 4–12 MPa and compressive modulus of 100–500 MPa [15]). What is more, trabecular bones are given porous structures which have a porosity of 50–90% [16] and average pore size of 600 µm [17]. However, several studies [18], [19] reported that nanoparticles served as nucleation points led to the formation of a large number of smaller cells in composite polyurethane foams. This might result in an inadequate pore size of a bone scaffold for bone ingrowth and vascularization. Finally, other studies reported that the SMP composites with physically-blended nanoparticles showed that the enhanced mechanical properties were often accompanied by the sacrifice of shape memory effects because of the agglomeration of nanoparticles in the SMP matrix. For example, in our previous study, the shape recovery ratio of SMPU decreased from 76.8% to 43.6% in the presence of 7% multi-walled carbon nanotubes [20]. In polyurethane/carbon black system containing 30 wt% of carbon black, the shape recovery ratio of the composite reduced from 98% to 65% [21]. It was also found that clay particles in polyurethane, reducing shape fixity ratio from 78% to 57% at 5 wt% of clay [22].
SMPU foams with chemically modified HA nanoparticles are promising materials to achieve the challenging goal of meeting conflicting requirements of bone scaffolds in pore structure, mechanical integrity, and shape memory performance. HA, a major inorganic component of bone, has been widely used for treatment of bone defects [14]. Shape memory polyurethane is chosen due to the fact that it has high shape memory performance, and biological and chemical compatibility to human tissue [23]. Polyurethane/HA composite foams for bone regeneration have been studied [14], [23], [24], [25]; however, the relationship between shape memory effects and HA nanoparticle has hardly been addressed, not mentioning chemically-incorporated HA in SMPU.
In the study, we designed composite SMPU foams with imHA nanoparticles as bone scaffolds for minimally invasive bone regeneration (Fig. 1). The chemically-incorporated HA nanoparticles act as inorganic crosslinkers to consolidate the SMPU structure and fillers. With all careful consideration and optimal combination, a systematic study was carried out on the SMPU/imHA foams in terms of pore structure, mechanical properties, shape memory performance and cytotoxicity in order to combine shape memory polymer foams and bone regeneration application.
Section snippets
2.1. Preparation of imHA nanoparticles
Polycaprolactone (PCL) with molecular weight (Mn) of 3000 was purchased from Perstorp Chemicals Co. Ltd. HA nanoparticles with a particle size of 20 nm were purchased from Emperor Nano Material Co. Ltd. All other chemicals and solvents were purchased from Sigma-Aldrich Co. Ltd. The imHA nanoparticles were prepared by casting HA nanoparticles in HDI solution (50 mg/mL). After 24 h stirring at room temperature, the samples were centrifuged and washed with dichloromethane to remove the residual HDI.
3.1. Chemical structure of imHA nanoparticles
HA nanoparticles were successfully modified by grafting HDI, as determined by the new chemical bonds appearing in FT-IR spectrum of imHA (Fig. 4). The ester absorption band of –C(=O)-O– at 1255 cm−1 resulted from the coupling reaction between the isocyanate group of HDI and the hydroxyl group of HA. It is also worth noting that there were peaks observed at 1716 and 1570 cm−1, which were assigned to the urethane carbonyl band and the amide band of imHA, respectively. These results indicated the
Conclusions
We designed a type of smart SMPU composite foam with chemically-incorporated imHA nanoparticles for bone scaffolds with a minimally invasive function. Results demonstrated the effectiveness of imHA nanoparticles as inorganic crosslinkers and fillers in SMPU foams in terms of solving conflicting factors (between pore structures and mechanical properties, and between mechanical properties and shape memory effects) to achieve a type of promising bone scaffold. As a whole the SMPU/imHA foams have
Acknowledgements
The research was funded by the National Natural Science Foundation of China (Grant No. 51373147), the Hong Kong General Research Fund (RGC Project No. 15209815) and Shenzhen Research Fund (Project No. JC201104210132A).
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